DESCRIPTION: The Women and Infants Transmission Study (WITS) enrolls HIV-infected pregnant women and their infants into a multicenter, epidemiologic cohort study whose objectives are to answer critical questions relevant to vertical transmission, and to HIV disease during pregnancy and infancy. In addition, research issues relevant to implementation of therapeutic intervention in this population will be addressed. The specific aims of WITS are to 1) Determine mechanisms of perinatal HIV transmission and maternal cofactors related to transmission including the role of maternal drug use, the role of the placenta, the role and characteristics of HIV in the birth canal, and of maternal coinfections; 2) Evaluate factors related to successful perinatal HIV prevention strategies, and intensely assess transmission cases that occur despite perinatal use of antiretrovirals; 3) Determine the impact of pregnancy on disease progression of HIV infection among women through the postpartum period, including immunologic and virologic changes in pregnancy; 4) Characterize acute HIV infection among HIV-infected children in light of antiretroviral, prophylactic and immune-based therapy; 5) Determine factors predicting pediatric disease progression among the cohort of HIV infected children in WITS. A Boston/Worcester consortium of investigators seeks to continue participation in WITS, utilizing the same experienced investigators and field staff that have successfully accrued over 300 pregnant women and over 250 HIV-at risk infants to date. The applicants propose to expand on the considerable expertise of the co-investigators by the addition of basic science consultants as well as two specific scientific collaborations. They propose 1) The utilization of new and sensitive techniques to perform a detailed analysis of CTL responses to pediatric HIV infection that will be helpful in understanding the pathogenesis and progression of perinatal HIV infection as well as insights to guide immunotherapeutic intervention; and 2) To explore the pathogenesis of vertical transmission in relation to both ontogeny of expression of CC chemokine receptor genes and also to receptor - tropism of particular strains of transmitted virus.